OAS1 induces endothelial dysfunction and promotes monocyte adhesion through the NFκB pathway in atherosclerosis.

Cardiovascular disease is characterized by chronic inflammation and atherosclerosis (AS) is the pathological basis. Mitigating endothelial dysfunction and mononuclear cell adhesion is a crucial approach in impeding the initial advancement of AS. As an inflammation-immune regulation-related protein, 2'-5'-oligoadenylate synthetase 1 (OAS1) plays a critical role in inflammation, but its impact on endothelial dysfunction and mononuclear cell adhesion is not well understood. In this study, bioinformatic analysis revealed a significant enrichment of OAS1 in atherosclerotic plaques within human aortic sections. In addition, OAS1 was detected in atherosclerotic plaques within human aortic sections across various stages of development, with elevated expression observed in more advanced plaques. The expression of OAS1 exhibited a distinct temporal and concentration-dependent upregulation in response to lipopolysaccharide (LPS) stimulation. Notably, the deficiency of OAS1 markedly attenuated the elevation in reactive oxygen species (ROS) levels, nitric oxide (NO) concentrations, and monocyte adhesion induced by LPS. A positive correlation was observed between the levels of NFκBp65 and OAS1 in human plaques, and the deletion of OAS1 led to a down-regulation of P65 expression. Furthermore, the simultaneous knockdown of OAS1 and NFκBp65 resulted in a significant amelioration of endothelial dysfunction (including ROS, NO, and inflammation factors) and monocyte adhesion, suggesting a synergistic interaction between OAS1 and NFκBp65. These findings underscore the potential of OAS1 to modulate the extent of endothelial dysfunction and monocyte adhesion through its regulation of NFκBp65 thereby positioning it as a promising therapeutic target for the management of AS.